2.6: Establishing Quality Control - The Essentials

Every company develops a routine way of doing things, but what happens when the way they are doing things no longer works for reasons out of their control? What if the market changes? What happens when the customer needs change? What about the needs of their workforce? How an organization adapts to a rapidly changing market and customer base is crucial to its survival.

Process & Process Improvement

A process collects inputs and provides value-added activities on those inputs to create an output. We do this every day without even realizing it. For example, we want to repaint our bedroom – what color to choose, the type of paint to use, the rollers, and who will perform the job? In our everyday life, most processes develop over time without any thought of their effectiveness, and the same happens with businesses. Companies must identify the processes and determine their effectiveness. Ineffectual or wasteful processes must be removed or changed for a business to stay successful.

Variation

Variation is a natural part of any process. Scientists have now discovered that even identical twins have small differences in their genetic makeup. Therefore, it goes with the production of a product. There are rarely two products exactly alike; there is always some small amount of variation. Companies interested in providing quality products use quality techniques to study the variation present in their process. When they discover the source of the variation, they can move toward a more consistently produced, higher quality product.

Specifications

Specifications are substantive requirements provided by the customer. There are many forms specifications can take depending on the product produced and its target customer. Specifications are descriptions that define and characterize properties that a product must possess for its intended use. There are specifications for both raw materials and products. As quoted from an FDA document (Guideline on General Principles of Process Validation, Food and Drug Administration, 1987):

"The desired product should be carefully defined regarding its characteristics, such as physical, chemical, electrical, and performance characteristics…It is important to translate the product characteristics into specifications as a basis for description and control of the product."

The table below provides an example of the broad range of specifications for the same chemical, in this case, sodium chloride. Notice the purity differences, the physical requirements, and additives – these specifications are based on the intended use.

Sodium Chloride Specification table. Table by J. O’Grady, CC BY 4.0.

Specification	Road Salt	Table Salt	Analytical Grade Salt
Chemical Purity	minimum 95%	minimum 97%	minimum 99%
Color	clear to white, yellow, red, black	clear to white	clear to white
Maximum Allowed in Contaminants	not specified	As 0.5 ppm Cu 2.0 ppm Pb 2.0 ppm Cd 0.5 ppm Hg 0.10 ppm	Al < 0.0005% As < 0.0001% Ba < 0.0005% Ca < 0.002% Cu < 0.0005%
Physical Requirement	90% of crystals between 2.36mm and 12.5 mm	90% of crystals between 0.3 mm and 1.4 mm	95% of crystals between 0.18mm and 0.3 mm
Allowed Additives	anti-caking agents of 5-100 ppm, Sodium Ferrocyanide, Ferric Ferrocyanide	coating agents, hydrophobic agents	not allowed
Moisture	2-3%	< 3%	not specified

These specifications illustrate several important points:

1. Properties that are necessary for that product based on its intended purpose.
2. The specifications for the same property may vary depending on the intended use.
3. Specifications always are associated with analytical methods.

It is important, for example, that road salt is not used for cake salt. Table salt is stored in containers that are open to the air, so it is important to include agents that absorb moisture from the air instead of the salt. These hygroscopic agents must be excluded from the analytical grade salt. Additionally, analysis of the analytical grade salt shows that it is free of contaminating metals as it may be used in techniques that are ruined by metal contamination or in techniques where the instrumentation would detect the metals, thereby interfering with the intended measurements. Sodium chloride could be a raw material for a biomanufacturing company. It is important that specifications for it are determined, documented, and a contract between the supplier and the company based on those specifications is established.

The Term "Establishing Specifications" Means:

1. Defining the characteristics of the product, material, or process
2. Documenting those specifications
3. Ensuring that the specifications are met

It is very important to establish specifications during the development of the product, for the product itself, all raw materials, and the process as part of the application to the FDA. This is not a simple task. It requires knowledge of how the product, materials, or process will be used, the properties that will make it suitable for that use, and the allowable ranges. If the range for a specification is too stringent, then adequate materials might be rejected. On the other hand, if the range of values for the specifications is too broad, then the quality of the product is not protected. Because the setting of specifications is both a critical component of a quality program and a challenging task, the FDA scrutinizes specifications for products it regulates.

The FDA will not accept specifications if they are not complete, if they are unsuitable for the product, if their range is too broad, if they are unsubstantiated by testing, or if suitable analytical methods to test them are not available.

Tolerance Limits

Tolerance Limits are the permissible changes in the specification. A product’s process is ‘under control’ when the specification is met within the tolerance limits provided by the customer.

Out of Specification

If samples do not satisfy specifications, then they are out-of-specification (OOS). If this occurs, operators may follow a procedure to correct the problem, or they may initiate an investigation. The FDA recognizes that from time to time, a batch of a product will be found not to meet all product release criteria. However, the FDA expects that the batch is not just thrown away but that the company must know why the batch did not meet requirements and determine if the “failure” is an isolated, explainable incident, or an indication of a significant problem associated with the manufacturing and control of a drug. This “explanation” must be in writing, supported by evidence, and reviewed by management and approved by at least QA. OOS laboratory data may be the result of lab error, non-process error or operator mistake (i.e., used wrong raw material or ingredient did not correctly follow manufacturing instructions) or process problem (i.e., equipment malfunction or process too variable or fundamentally flawed).

Productivity

Productivity may be defined as working effectively while best utilizing the available resources. Productivity is a little different from quality, which focuses on effectiveness – achieving goals while meeting customer needs. Improvements in productivity and quality come from managing the work activity regarding processes. Measuring the effectiveness of processes helps identify areas of increased productivity.